Photothermal vascular targeting with bioreductive agents

Abstract

A method of selectively enhancing the effect of photothermal vascular targeting on tumor regression by administration of a bioreductive agent is disclosed.

What is claimed is:  
     
       1. A method of treating a tumor characterized by nutrient-providing blood vessels comprising 
       irradiating the tumor or nutrient providing blood vessels in the presence of a bioreductive agent,  
       creating an environment of hypoxia for the bioreductive agent, and  
       allowing the bioreductive agent to act as a cytotoxic agent in a manner to reduce tumor size.  
     
     
       2. A method of treating a tumor characterized by nutrient-providing blood vessels comprising 
       exposing the tumor to a bioreductive agent,  
       exposing the tumor to a light source,  
       denaturing the nutrient-providing blood vessels by exposing the blood vessels to the light source,  
       creating an environment of hypoxia for the bioreductive agent, and  
       allowing the bioreductive agent to act as a cytotoxic agent in a manner to reduce tumor size.  
     
     
       3. The method of claim  2  wherein said light source is at a wavelength corresponding to that absorbed by endogenous chromophores. 
     
     
       4. The method of claim  3  wherein said wavelength is between about 560 nm to about 610 nm. 
     
     
       5. The method of claim  3  wherein said wavelength is between about 570 nm to about 600 nm. 
     
     
       6. The method of claim  3  wherein said wavelength is between about 585 nm to about 590 nm. 
     
     
       7. The method of claim  2  wherein said bioreductive agent is porfiromycin or mitomycin C. 
     
     
       8. The method of claim  2  wherein said light source has a pulse duration less than a thermal relaxation time of a volume of the tumor and nutrient-providing blood vessels. 
     
     
       9. The method of claim  8  wherein said pulse duration is between about 0.1 msec to about 60 msec. 
     
     
       10. The method of claim  8  wherein said pulse duration is between about about0.1 msec to about 10 msec. 
     
     
       11. The method of claim  8  wherein said pulse duration is between about 0.3 msec to about 0.5 msec. 
     
     
       12. The method of claim  2  wherein said light source is a laser. 
     
     
       13. The method of claim  12  wherein said laser is a pulsed dye laser. 
     
     
       14. The method of claim  13  wherein said pulsed dye laser has a fluence between about 1 J/cm 3  to about 30 J/cm 3 . 
     
     
       15. The method of claim  13  wherein said pulsed dye laser has a fluence between about 5 J/cm 3  to about 15 J/cm 3 . 
     
     
       16. The method of claim  13  wherein said pulsed dye laser has a fluence of about 10 J/cm 3 . 
     
     
       17. A method of treating a tumor characterized by nutrient-providing blood vessels comprising 
       exposing the tumor to a bioreductive agent,  
       exposing the nutrient-providing blood vessels to an exogenous photoactivated compound,  
       denaturing the nutrient-providing blood vessels by exposing the blood vessels to a light source at a wavelength corresponding to that absorbed by the exogenous photoactivated compound,  
       creating an environment of hypoxia for the bioreductive agent, and  
       allowing the bioreductive agent to act as a cytotoxic agent in a manner to reduce tumor size.  
     
     
       18. The method according to claim  17 , wherein said photoactivated compound is iodocyanine green. 
     
     
       19. The method of claim  17 , wherein said photoactivated compound is a bioreductive agent. 
     
     
       20. A method of treating a tumor characterized by nutrient-providing blood vessels comprising 
       exposing the tumor to a bioreductive agent,  
       denaturing the nutrient-providing blood vessels by exposing the blood vessels to a pulsed dye laser at a wavelength corresponding to that absorbed by endogenous chromophores, wherein said pulsed dye laser has a pulse duration less than a thermal relaxation time of a volume of the nutrient-providing blood vessels,  
       creating an environment of hypoxia for the bioreductive agent, and  
       allowing the bioreductive agent to act as a cytotoxic agent in a manner to reduce tumor size.